The focus of this work has been to understand the molecular details that control the interaction of MHC molecules with NK receptors, T cell receptors, and with coreceptors such as CD8. These studies are dependent upon structural, functional, and biophysical analysis of the interaction of the molecules in question, and attempts are made to correlate binding properties with function and structure. Progress in the past year has been particularly fruitful with respect to our understanding of MHC-I-like molecules encoded by cytomegaloviruses. In particular, we have cloned, expressed, purified, crystallized, and determined the three-dimensional structure to 1.9 A resolution of the first example of an MHC-I-like molecule encoded by the murine cytomegalovirus, m144. This reveals a molecule that lacks bound peptide, maintains the major MHC-I fold, but has unique structural features that contribute to thermal stability. Mutagenesis experiments confirm the importance of a unique disulfie bond of this molecule. In addition, we have examined the cellular expression of three additional cytomegalovirus MHC-Iv immunoevasins, M37, m151, and m153. Each of these has unique cell biological features. Studies are underway to explore the biochemistry, cellular immunology, and structure of each of these unique, virus-encoded receptors.